The long range objective of this project is to carefully re-examine the nature of binding specificity at antibody combining regions and other types of receptor sites. The effects of polyvalent binding on binding energy and specificity will be considered, and together these properties will be related to the behavior of immune systems. In particular, multispecific binding of disparate structures by individual antibody species is being studied through screening of specifically purified, radiolabeled antibodies with affinity chromatography columns. The ligands are bound to these columns using large haptenic reagents synthesized specially for this purpose using methods of peptide synthesis. Multispecific binding will be used for producing and isolating homogeneous antibody by cross-stimulation and immunoadsorption. A number of chemical techniques and products that have been developed from the above work are being used in collaborative studies on molecular interpretation of cellular mechanisms in immune responses. Materials employed include synthetic thymus-independent antigens.